In this proposal we will study the effects of elevated CSF pressures on CSF outflow resistance and ultrastructural changes in the arachnoid villus of adult cats. Elevated CSF steady state pressures (CSFSSP) will be achieved using a series of constant rate infusions of artificial CSF into the subarachnoid space. The resultant quantitative changes in outflow resistance and conductance at different levels of CSFSSP will be correlated with structural changes in the arachnoid villus at each level of increasing CSF pressure. Pressure-induced alterations of pinocytotic vesicles contained within the arachnoid villus endothelium will be examined using a series of constant rate infusions of a horseradish or microperoxidase solution achieving several levels of CSFSSP. Pressure induced alterations of the structural and permeability characteristics of endothelial tight junctions will also be analyzed using infusions of horseradish peroxidase and microperoxidase at similar levels of CSF pressure. The experimental induction of subarachnoid hemorrhage will be used as a model for the study of pathologic effect of blood or its separate components on CSF transport through arachnoid villus. After the infusion of either whole blood, red blood cells, plasma, or serum into the subarachnoid space, the acute and long term effects of these substances on outflow resistance will be quantified using the monametric infusions of artificial CSF. Acute and chronic structural changes in the arachnoid villus, including the endothelium, will be described and the results compared with those obtained in our study of the normal and pressure stressed CSF outflow pathway at the arachnoid villus.